Hypoglycemia in the ICU has been associated with increased mortality in a number of studies. Insulin dosing and glucose monitoring rules, response to impending hypoglycemia, use of computerization, and attention to modifiable factors extrinsic to insulin algorithms may affect the risk for hypoglycemia. Recurring use of intravenous (IV) bolus doses of insulin in insulin-resistant cases may reduce reliance upon higher IV infusion rates. In order to reduce the risk for hypoglycemia in the ICU, caregivers should define responses to interruption of continuous carbohydrate exposure, incorporate transitioning strategies upon initiation and interruption of IV insulin, define modifications of antihyperglycemic therapy in the presence of worsening renal function or chronic kidney disease, and anticipate the effects traceable to other medications and substances. Institutional and system-wide quality improvement efforts should assign priority to hypoglycemia prevention.

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Design features that may mitigate risk for hypoglycemia include use of a mid-protocol bolus feature and establishment of a low BG threshold for temporary interruption of infusion. Computer-guided dosing may improve target attainment without exacerbating risk for hypoglycemia. Column assignment (MR) within a tabular user-interpreted algorithm or multiplier may be specified initially according to patient characteristics and medical condition with revision during treatment based on patient response. We hypothesize that a strictly increasing sigmoidal relationship between MR-dependent IR and BG may reduce risk for hypoglycemia, in comparison to a linear relationship between multiplier-dependent IR and BG. Guidelines are needed that curb excessive up-titration of MR and recommend periodic pre-emptive trials of MR reduction. Future research should foster development of recommendations for "protocol maxima" of IR appropriate to patient condition.

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